Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery

This paper describes the development of pH-sensitive poly(methyl methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical products for oral administration. To obtain the dissolution at the desired pH level, different pH-sensitive polymers are available on the market. Usually, for each desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH values could ask for completely different polymers. Instead, the materials proposed in this work are copolymers of the same two monomers, and the different dissolution pH was obtained by changing the volume fraction of the hydrophobic methyl methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the volumetric percentage of methyl methacrylate causes the polymer to dissolve at increasing pH, until the dissolution does not take place at all, and it is replaced by a slow swelling phenomenon. The copolymers obtained were characterized by differential scanning calorimetry, in order to evaluate their glass transition temperature, and these latter were related to %MMA. The molecular weights of the pure polymers (PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass transition temperatures observed. The dissolution of the copolymers was carefully tested in buffer solutions for a dense set of pH values. A linear relationship between dissolution pH and volumetric percentage of methyl methacrylate was obtained from these measurements. As a result, for any physiological compartment, the copolymer which dissolves at the pH of interest can be easily synthesized.     

Effects of polymer modification on the fuel resistance of asphalt binders

Fuel resistance is an important characteristic of asphalt binders, especially when used in airport fields and filling stations. However, the relevant standards are presently lacking and the scientific literature on the development of suited formulations is sparse. In this paper, a simple procedure to assess the fuel resistance of asphalts (considered in a dynamic sense) is proposed. A number of polymer modified asphalts (PMAs), prepared from two bases and 4 or 6 wt% of several polymers, have been analyzed with this procedure and the relationships between fuel resistance and morphology of the PMAs, the chemical structure of the polymers and the composition of the asphalt bases have been investigated.     

Assessment of the load-carrying capacity of multi-span masonry arch bridges using fibre beam elements

An approach that makes use of non-linear beam elements with fibre cross-section has been used for modelling the ultimate behaviour of multi-span masonry arch bridges. The proposed approach proves able to take into account the interaction among the spans and the non-linear material behaviour with low computational effort. In order to validate the use of the model for the assessment of masonry arch bridges, the load-carrying capacity for typical multi-span railway bridges has been evaluated and the results compared to experimental results and to currently used limit analysis methods. It is shown that, by parity of constitutive assumption, the method provides the same results as limit analysis, both in terms of maximum load prediction and hinges position at collapse; however, taking the effective ductility capacity into account, a strong reduction in load-carrying capacity with respect to classical limit analysis was found, depending on rise-to-span arch ratio, piers slenderness and backfill height. The approach is then applied to a seven span viaduct of the Italian railway network, for which the effective mechanical properties of masonry were identified through an experimental campaign on brickwork samples according to the effective material properties surveyed on site.     

Reversing the Psychiatric Effects of Neurodevelopmental Cannabinoid Exposure: Exploring Pharmacotherapeutic Interventions for Symptom Improvement

Neurodevelopmental exposure to psychoactive compounds in cannabis, specifically THC, is associated with a variety of long-term psychopathological outcomes. This increased risk includes a higher prevalence of schizophrenia, mood and anxiety disorders, and cognitive impairments. Clinical and pre-clinical research continues to identify a wide array of underlying neuropathophysiological sequelae and mechanisms that may underlie THC-related psychiatric risk vulnerability, particularly following adolescent cannabis exposure. A common theme among these studies is the ability of developmental THC exposure to induce long-term adaptations in the mesocorticolimbic system which resemble pathological endophenotypes associated with these disorders. This narrative review will summarize recent clinical and pre-clinical evidence that has elucidated these THC-induced developmental risk factors and examine how specific pharmacotherapeutic interventions may serve to reverse or perhaps prevent these cannabis-related risk outcomes.     

Preliminary diagnostic evaluation of submucosal myoma using operative hysteroscopy

BACKGROUND AND AIM: The authors aim to underline the importance of preliminary diagnostic evaluation in the treatment of submucous leiomyoma using hysteroscopy. MATERIALS AND METHODS: The study examined 18 patients monitored at the Institute of Obstetrics and Gynecology of "La Sapienza" University of Rome between January and December 1995 in whom it was possible to make a correct definition of the lesion to be treated (number, site, size, etc.) using 3 different diagnostic methods: hysteroscopy (HS), transvaginal scan (TSV) and transvaginal echohysterography (TVHS) The authors focused attention on three different parameters: leiomyoma size, extension (intracavity/intramural portion) and evaluation of the residual leiomyoma, which are essential for optimal endoscopic resection. RESULTS: HS enabled the number, size, site, origin, base, submucous portion and relations with tube operings to be evaluated, but did not allow the myometrial part of the lesion to be examined. CONCLUSIONS: Integration with TSV, even if this does not allow a precise definition of the extension, highlights the size, site, involvement of myometrial structure and relations with the perimetrium, thus allowing the possibility of evaluating the residual myometrium. Compared to the above methods, TVHS highlights the effective extension (namely the submucous/intramural portion) and localization of the neoformation.     

Neural-fuzzy optimization of thick composites curing process

This article addresses the optimization of curing process for thick composite laminates. The proposed methodology aims at the evaluation of the thermal cycle promoting a desired evolution of the degree of cure inside the material. At the same time, temperature overshooting as well as excessive temperature and cure degree gradient through the thickness of the material are prevented. The developed approach is based on the integrated application of artificial neural networks and a fuzzy logic controller. The neural networks promptly predict the behavior of composite material during curing process, while the fuzzy logic controller continuously and opportunely adjusts the proper variations on the imposed thermal cycle. The results highlighted the efficiency of the method in comparison with the cure profiles dictated by the material suppliers. For thick laminates, a reduction of 35% of cure time and improvements of approximately 10% of temperature overshooting was obtained compared to conventional curing cycles. The method was validated by experimental tests.     

Potential of different additives to improve performance of potassium carbonate for CO<Subscript>2</Subscript> absorption

The performance of potassium carbonate (K₂CO₃) solution promoted by three amines, potassium alaninate (K-Ala), potassium serinate (K-Ser) and aminoethylethanolamine (AEEA), in terms of heat of absorption, absorption capacity and rate was studied experimentally. The experiments were performed using a batch reactor, and the results were compared to pure monoethanolamine (MEA) and K₂CO₃ solutions. The heat of absorption of K₂CO₃+additive solution was calculated using the Gibbs-Helmholtz equation. In addition, a correlation for prediction of CO₂ loading was presented. The results indicated that absorption heat, absorption rate and loading capacity of CO₂ increase as the concentration of additive increases. The blend solutions have higher CO₂ loading capacity and absorption rate when compared to pure K₂CO₃. The heat of CO₂ absorption for K₂CO₃+additive solutions was found to be lower than that of the pure MEA. Among the additives, AEEA showed the highest CO₂ absorption capacity and absorption rate with K₂CO₃. In conclusion, the K₂CO₃+AEEA solution with high absorption performance can be a potential solvent to replace the existing amines for CO₂ absorption.     

Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) ({"type":"clinical-trial","attrs":{"text":"NCT02195726","term_id":"NCT02195726"}}NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.     

Take a Break to Repair: A Dip in the World of Double-Strand Break Repair Mechanisms Pointing the Gaze on Archaea

All organisms have evolved many DNA repair pathways to counteract the different types of DNA damages. The detection of DNA damage leads to distinct cellular responses that bring about cell cycle arrest and the induction of DNA repair mechanisms. In particular, DNA double-strand breaks (DSBs) are extremely toxic for cell survival, that is why cells use specific mechanisms of DNA repair in order to maintain genome stability. The choice among the repair pathways is mainly linked to the cell cycle phases. Indeed, if it occurs in an inappropriate cellular context, it may cause genome rearrangements, giving rise to many types of human diseases, from developmental disorders to cancer. Here, we analyze the most recent remarks about the main pathways of DSB repair with the focus on homologous recombination. A thorough knowledge in DNA repair mechanisms is pivotal for identifying the most accurate treatments in human diseases.